Perturbation of cells by tumor viruses has been used as a probe of the various growth controls by which normal tissues maintain a constant cell mass. One potent, well-studied class of these tumor viruses is the DNA containing Simian virus 40 (SV40). Susceptibility of human skin fibroblasts to SV40 infection has been suggested as a marker of cancer risk. Through the use of this viral probe we propose to gain insight about the nature of phenotypic expressions associated with cancer development and about the increased genetic susceptibility to cancer of individuals at risk. These studies will be carried out on fibroblastic cells isolated from normal-appearing skin obtained from individuals with hereditary adenomatosis of the colon and rectum (ACR), an autosomal dominant trait. We have previously demonstrated the appearance in these fibroblasts of abnormal phenotypic expressions which often occur in the transformed phenotype. We have also shown that these cells were more sensitive to transformation by the Kirsten murine sarcoma virus (KiMSV) and to the expression of SV40-induced T antigen display (present grant). We shall examine the effects of SV40 on the following cellular parameters associated with cell transformation and malignancy: a) cell proliferation, b) chromosomal aberrations, c) mutagenesis, d) cell differentiation, e) abnormal phenotypic expressions associated with the transformed phenotype, and f) malignant transformation. We shall further study the suitability of this viral probe as a possible marker of latent ACR.